{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,15]],"date-time":"2026-09-15T07:07:22Z","timestamp":1789456042992,"version":"build-2803163510"},"reference-count":40,"publisher":"Wiley","issue":"17","license":[{"start":{"date-parts":[[2026,9,7]],"date-time":"2026-09-07T00:00:00Z","timestamp":1788739200000},"content-version":"vor","delay-in-days":6,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"},{"start":{"date-parts":[[2026,9,1]],"date-time":"2026-09-01T00:00:00Z","timestamp":1788220800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/doi.wiley.com\/10.1002\/tdm_license_1.1"}],"content-domain":{"domain":["onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["J Cellular Molecular Medi"],"published-print":{"date-parts":[[2026,9]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>Legg\u2010Calv\u00e9\u2010Perthes disease (LCPD) is an idiopathic paediatric osteonecrosis characterized by avascular injury to the femoral head, resulting in structural collapse and early osteoarthritis. Although mesenchymal stem cell (MSC) dysfunction has been implicated, the underlying mechanisms remain unclear due to the absence of human disease models. Here, we generated patient\u2010specific induced pluripotent stem cells (iPSCs) from dermal fibroblasts of LCPD patients and differentiated them into mesenchymal stem cells (iMSCs) to establish an in\u00a0vitro platform for mechanistic interrogation. LCPD\u2010iMSCs exhibited hallmark disease\u2010associated phenotypes, including concurrent suppression of osteogenic, adipogenic and chondrogenic differentiation, accompanied by enhanced phosphorylation of GSK3\u03b1\/\u03b2, reduced \u03b2\u2010catenin abundance and attenuated canonical Wnt signalling. Transcriptomic analyses revealed alterations in extracellular matrix organization, adhesion pathways and PI3K\u2010Akt\/MAPK signalling, consistent with a cellular environment predisposed to impaired mesenchymal function. Pharmacological inhibition of GSK3 using lithium chloride restored \u03b2\u2010catenin levels, improved osteogenic and adipogenic marker expression, and enhanced matrix deposition, demonstrating functional reversibility of the LCPD phenotype. These findings identify GSK3\u2010mediated \u03b2\u2010catenin destabilization as a central regulator of MSC lineage impairment in LCPD and establish a patient\u2010derived iPSC\u2010MSC model as a valuable platform for mechanistic and therapeutic exploration in paediatric osteonecrosis.<\/jats:p>","DOI":"10.1111\/jcmm.71350","type":"journal-article","created":{"date-parts":[[2026,9,8]],"date-time":"2026-09-08T04:28:56Z","timestamp":1788841736000},"update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":0,"title":["Patient\u2010Derived\n                    <scp>iPSC<\/scp>\n                    \u2010\n                    <scp>MSC<\/scp>\n                    Modelling Reveals Reversible\n                    <scp>GSK3<\/scp>\n                    \u2010Mediated Suppression of Mesenchymal Lineage Differentiation in Legg\u2010Calv\u00e9\u2010Perthes Disease"],"prefix":"10.1111","volume":"30","author":[{"given":"Binna","family":"Seol","sequence":"first","affiliation":[{"name":"Stem Cell Research Laboratory, Immunotherapy Research Center Korea Research Institute of Bioscience and Biotechnology (KRIBB)  Daejeon South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-9254-9196","authenticated-orcid":false,"given":"Hyung Jin","family":"Lim","sequence":"additional","affiliation":[{"name":"Stem Cell Research Laboratory, Immunotherapy Research Center Korea Research Institute of Bioscience and Biotechnology (KRIBB)  Daejeon South Korea"},{"name":"Department of Bioscience, KRIBB School University of Science &amp; Technology  Daejeon South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Cho Lok","family":"Song","sequence":"additional","affiliation":[{"name":"Stem Cell Research Laboratory, Immunotherapy Research Center Korea Research Institute of Bioscience and Biotechnology (KRIBB)  Daejeon South Korea"},{"name":"Department of Bioscience, KRIBB School University of Science &amp; Technology  Daejeon South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jungwoon","family":"Lee","sequence":"additional","affiliation":[{"name":"Department of Bioscience, KRIBB School University of Science &amp; Technology  Daejeon South Korea"},{"name":"Stem Cell &amp; Regenerative Biology Laboratory, Environmental Disease Research Center Korea Research Institute of Bioscience and Biotechnology (KRIBB)  Daejeon South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6224-6685","authenticated-orcid":false,"given":"Yee Sook","family":"Cho","sequence":"additional","affiliation":[{"name":"Stem Cell Research Laboratory, Immunotherapy Research Center Korea Research Institute of Bioscience and Biotechnology (KRIBB)  Daejeon South Korea"},{"name":"Department of Bioscience, KRIBB School University of Science &amp; Technology  Daejeon South Korea"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2026,9,7]]},"reference":[{"issue":"1","key":"e_1_2_9_2_1","first-page":"18","article-title":"Legg\u2010Calve\u2010Perthes Disease: An Overview With Recent Literature","volume":"72","author":"Chaudhry S.","year":"2013","journal-title":"Bulletin of the Hospital for Joint Diseases"},{"key":"e_1_2_9_3_1","doi-asserted-by":"publisher","DOI":"10.1016\/j.jos.2016.03.008"},{"key":"e_1_2_9_4_1","doi-asserted-by":"publisher","DOI":"10.1177\/18632521231203009"},{"key":"e_1_2_9_5_1","doi-asserted-by":"publisher","DOI":"10.3389\/fphys.2025.1514302"},{"key":"e_1_2_9_6_1","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199205283262206"},{"issue":"7","key":"e_1_2_9_7_1","first-page":"659","article-title":"Pathophysiology and New Strategies for the Treatment of Legg\u2010Calve\u2010Perthes Disease","volume":"94","author":"Kim H. 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